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Elucidation of molecular mechanism on thyroid carcinogenesis anddevelopmental application of molecular targeting therapy

甲状腺癌发生分子机制阐明及分子靶向治疗的发展应用

基本信息

批准号：
22390189
负责人：
YAMASHITA Shunichi
金额：
$ 11.32万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2012
项目状态：
已结题

项目摘要

We have successfully established a cell culture system from primary human thyroid tissues and identified the multi-potential stem cell-like cells in a specific serum-free medium condition. One speculates that there is a profound relationship of reprogramming and mesenchymal transition between stem cell-like cells and differentiated cells from thyroid tissues. These findings may suggest a new aspect and relationship of thyroid cancer stem cells during its carcinogenesis. Furthermore we have studied the functional role of FOXE1 that is a major thyroid cancer-associated SNP gene. Using immunohistochemistry, specific patterns of FOXE1 expression in thyroid carcinomas have been identified. We have separately clarified a strong association between the SNPs of FOXE1 and NKX-2, and the Japanese thyroid cancer cases. This is the first report on the different ethnics besides Caucasians. Finally we found the new evidence of imanitib, a molecular targeting agent, selectively inhibited an increase of NFkappa B activity induced by irradiation in cultured thyroid cancer cell lines. The combination chemotherapy with radiation may become more efficient therapeutic approach for a poor-prognosis thyroid anaplastic cancer patient clinically.

我们成功建立了人甲状腺原代组织的细胞培养体系，并在特定的无血清培养基条件下鉴定出多潜能干细胞样细胞。一种推测认为，甲状腺组织干细胞样细胞和分化细胞之间存在着重编程和间质转化的深刻关系。这些发现可能提示了甲状腺癌干细胞在其癌变过程中的一个新的方面和关系。此外，我们还研究了FOXE1的功能作用，FOXE1是一个主要的甲状腺癌相关SNP基因。利用免疫组织化学，FOXE1在甲状腺癌中的特异表达模式已经被确定。我们已经分别阐明了FOXE1和NKX-2的snp与日本甲状腺癌病例之间的强烈关联。这是除白种人外的第一个关于不同种族的报告。最后，我们发现了分子靶向剂伊曼尼布选择性抑制辐照诱导的甲状腺癌细胞NFkappa B活性升高的新证据。化疗加放疗可能成为临床上治疗预后不良甲状腺间变性癌的有效方法。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Image-based quantitative determination of DNA damage signal reveals a threshold for G2 checkpoint activation in response to ionizing radiation.

DOI：
10.1186/2041-9414-1-10
发表时间：
2010-08-04
期刊：
Genome integrity
影响因子：
0
作者：
Ishikawa A;Yamauchi M;Suzuki K;Yamashita S
通讯作者：
Yamashita S

Dedifferentiation of human primary thyrocytes into multilineage progenitor cells without gene introduction.

DOI：
10.1371/journal.pone.0019354
发表时间：
2011-04-27
期刊：
PloS one
影响因子：
3.7
作者：
Suzuki K;Mitsutake N;Saenko V;Suzuki M;Matsuse M;Ohtsuru A;Kumagai A;Uga T;Yano H;Nagayama Y;Yamashita S
通讯作者：
Yamashita S

Clustered DNA damage and ATM-dependent DNA damage checkpoint

簇状 DNA 损伤和 ATM 依赖性 DNA 损伤检查点